The present invention relates to a novel method for preparing arylamines which are useful intermediates and end products in pharmaceutical and agricultural applications. The present invention further relates to applications of the method.
The arylamine moiety is a structural component in a variety of synthetic and naturally occurring biologically active compounds. Methods to construct the carbon-nitrogen bond in arylamines, however, are limited. Many synthetic methods for the construction of such an aryl-nitrogen bond suffer from severe reaction conditions and/or are applicable only for activated substrates. Typical routes to aromatic amines include nucleophilic aromatic substitution of aryl precursors. See, Hattori et al. Synthesis 1994, 199 (1994); and Bunnett, J. F. Acc. Chem. a Res 1978 11,413 (1978). Synthesis of arylamines via copper-mediated Uhlmann condensation reactions also has been reported. See, Paine, A. J. J. Am. Chem. Soc. 1987, 109, 1496 (1987).
Migita and coworkers have described the preparation of N,N-diethylaminobenzenes from the palladium-catalyzed reaction of aryl bromides and N,N-diethylaminotributyltin. See, Kosugi et al. Chem. Lett. 1983, 927-928 (1983). However, the general applicability of this synthetic route is limited due to the high reactivity and instability of the aminostannanes (generally, R.sub.3 Sn(NR'.sub.2)). Jones and Lappert report that many aminostannanes are moisture sensitive, decompose or undergo a condensation reaction to form distannazane compounds (generally, (R.sub.3 Sn).sub.2 NR'). The high reactivity of aminostannanes may hinder their effective isolation and use in subsequent reactions. See, Jones, K. and Lappert, M. F. Organomet. Chem. Rev. 1966 (1), 67-92. Further, the use of aminostannanes is undesirable from an environmental standpoint because of their toxicity.
Boger and coworkers reported the formation of an aryl-nitrogen bond by reaction of an amine moiety with an aryl bromide without the use of a metal amide and, in particular, without the use of an aminostannane. However, the reaction required the use of stoichiometric amounts of palladium(0) in order for the reaction to occur. See, Boger et al. J. Org. Chem. 1985 50, 5782.
A general route to a wide range of arylamines under moderate reaction conditions is yet to be reported. Therefore, it is an object of the present invention to provide such a general synthetic route to a wide range of arylamines. It is a further object of the present invention to provide a synthetic route to arylamines which do not require the use of aminostannanes. It is a further object of the present invention to apply the method to obtain useful arylamine derivatives and polymers.